crossing96/oncoscreening huggingface dataset:
Smoking status, usual adult occupation, and risk of recurrent urothelial bladder carcinoma: data from The Cancer Genome Atlas (TCGA) Project.	PURPOSE: Tobacco smoking and occupational exposures are the leading risk factors for developing urothelial bladder carcinoma (UBC), yet little is known about the contribution of these two factors to risk of UBC recurrence. We evaluated whether smoking status and usual adult occupation are associated with time to UBC recurrence for 406 patients with muscle-invasive bladder cancer submitted to The Cancer Genome Atlas (TCGA) project. METHODS: Kaplan-Meier and Cox proportional hazard methods were used to assess the association between smoking status, employment in a high-risk occupation for bladder cancer, occupational diesel exhaust exposure, and 2010 Standard Occupational Classification group and time to UBC recurrence. RESULTS: Data on time to recurrence were available for 358 patients over a median follow-up time of 15 months. Of these, 133 (37.2%) experienced a recurrence. Current smokers who smoked for more than 40 pack-years had an increased risk of recurrence compared to never smokers (HR 2.1, 95% CI 1.1, 4.1). Additionally, employment in a high-risk occupation was associated with a shorter time to recurrence (log-rank p = 0.005). We found an increased risk of recurrence for those employed in occupations with probable diesel exhaust exposure (HR 1.8, 95% CI 1.1, 3.0) and for those employed in production occupations (HR 2.0, 95% CI 1.1, 3.6). CONCLUSIONS: These findings suggest smoking status impacts risk of UBC recurrence, although several previous studies provided equivocal evidence regarding this association. In addition to the known causal relationship between occupational exposure and bladder cancer risk, our study suggests that occupation may also be related to increased risk of recurrence.	bladder
[Development of a Drug Delivery System for Cancer Immunotherapy].	Delivery systems are a powerful technology for enhancing the effect of cancer immunotherapy. We have been in the process of developing lipid-based delivery systems for controlling the physical properties and dynamics of immunofunctional molecules such as antigens and adjuvants. The lipid nanoparticulation of these molecules improves their physical properties, resulting in a good water dispensability, greater stability, and small size. The cell wall skeleton of bacille Calmette-Guerin (BCG-CWS) could be used to replace live BCG as a drug for treating bladder cancer, but problems associated with the physical properties of BCG-CWS have prevented its use. To overcome such problems, we developed a novel packaging method that permits BCG-CWS to be encapsulated into lipid nanoparticles, which induce antitumor responses against bladder cancer. Lipid nanoparticulation also improves the intracellular trafficking and biodistribution of immunofunctional molecules. Cyclic di-GMP (c-di-GMP) is an adjuvant that is recognized by the cytosolic sensor. However, c-di-GMP cannot pass through the cell membrane. We encapsulated c-di-GMP into lipid nanoparticles containing a pH-responsive lipid that was developed in our laboratory and achieved efficient cytosolic delivery and the induction of antitumor immunity. Furthermore, we are attempting to control the functions of immune cells by RNA interference. We have recently succeeded in the efficient delivery of small interfering RNA into mouse dendritic cells (DCs), which led to the enhancement of antitumor activity of DCs. In this review, our recent efforts regarding cancer immunotherapy using lipid-based nanoparticles are reviewed.	bladder
High-Risk of Adverse Pathologic Features in Patients With Clinical T1 High-Grade Bladder Cancer Undergoing Radical Cystectomy.	BACKGROUND: Radical cystectomy (RC) is used to treat select patients with T1 high-grade (T1HG) bladder cancer. However, population-level utilization trends and outcomes for these patients are not well-known. We sought to evaluate treatment patterns and clinicopathologic outcomes of RC for T1HG bladder cancer. PATIENTS AND METHODS: Using the National Cancer Data Base (NCDB) for 1998-2012, we conducted a retrospective cohort study of patients with clinical T1HG bladder cancer. The prevalence of RC used to treat T1HG bladder cancer from 1998-2012 was determined. For years 2010-2012, demographic and cancer-related factors were described and regression analysis was used to examine associations with RC. Oncologic outcomes of RC were described and related to mortality using Cox proportional hazards regression. RESULTS: Treatment of T1HG bladder cancer with RC nearly doubled, from 5.5% during 1998-2000 to 9.9%, during 2010-2012. For 2010-2012, 18,277 patients with T1HG bladder cancer were analyzed. Patients who underwent RC were younger, had fewer comorbidities, and were more often treated at an academic center than those who did not undergo RC. At the time of RC, 41% of patients with T1HG bladder cancer were upstaged (pT2 or greater) and 12.7% had lymph node metastases. The 1- and 3-year survival rates were 0.89 and 0.68, respectively. Extravesical (T3+) disease at RC had the strongest independent hazard (hazard ratio [HR], 2.32; 95% CI, 1.72-3.11) of death other than age of 82 years or older (HR, 3.40; 95% CI, 2.28-5.07). CONCLUSIONS: The use of RC for T1HG bladder cancer has increased in prevalence in recent years but is still not widely used. There are concerning pathologic outcomes in patients with clinical T1HG bladder cancer treated with RC, including high rates of pathologic upstaging and nodal metastases. Future studies are necessary to better risk-stratify patients with T1HG bladder cancer to best select those who will benefit from aggressive therapy with RC.	bladder
Evaluation of conservative approach in the management of ureteroenteric strictures following radical cystectomy with Bricker ileal conduit: a single-center experience.	OBJECTIVE: The aim of this study was to evaluate the risk factors and treatment options for ureteroenteric strictures (UES) following radical cystectomy (RC) and ileal conduit (IC) formation, and specifically to comment on the conservative management of UES in asymptomatic patients. MATERIALS AND METHODS: The datasheets were reviewed of 304 consecutive patients who were treated with an RC and IC between January 2001 and May 2011 in a Belgian tertiary center and who followed a strict follow-up protocol. Long-term treatment outcomes were retrospectively analyzed. RESULTS: Twenty-two patients (7.2%) were diagnosed with UES (affecting 27 ureters in total), when a new-onset hydroureteronephrosis or increase of the pre-existing hydroureteronephrosis was detected by ultrasound or computed tomography. A retrograde loopogram was then performed to confirm the UES. The mean follow-up time was 33 months. A decline in renal function, the presence of flank pain and urinary tract infections were indications for interventional treatment. Six patients underwent double-J stent placement, two patients received percutaneous nephrostomies as a definitive treatment and two patients underwent ureterointestinal reimplantation. Asymptomatic patients with a UES and a favorable renal function were conservatively managed. They remained asymptomatic during follow-up and required no active treatment. CONCLUSIONS: No clinical variable was independently associated with an increased risk of UES. These long-term data suggest that a selected patient population of asymptomatic patients with good renal function at the time of UES diagnosis can be safely managed conservatively.	bladder
Nitrate from Drinking Water and Diet and Bladder Cancer Among Postmenopausal Women in Iowa.	BACKGROUND: Nitrate is a drinking water contaminant arising from agricultural sources, and it is a precursor in the endogenous formation of N-nitroso compounds (NOC), which are possible bladder carcinogens. OBJECTIVES: We investigated the ingestion of nitrate and nitrite from drinking water and diet and bladder cancer risk in women. METHODS: We identified incident bladder cancers among a cohort of 34,708 postmenopausal women in Iowa (1986-2010). Dietary nitrate and nitrite intakes were estimated from a baseline food frequency questionnaire. Drinking water source and duration were assessed in a 1989 follow-up. For women using public water supplies (PWS) > 10 years (n = 15,577), we estimated average nitrate (NO3-N) and total trihalomethane (TTHM) levels and the number of years exceeding one-half the maximum contaminant level (NO3-N: 5 mg/L, TTHM: 40 μg/mL) from historical monitoring data. We computed hazard ratios (HRs) and 95% confidence intervals (CIs), and assessed nitrate interactions with TTHM and with modifiers of NOC formation (smoking, vitamin C). RESULTS: We identified 258 bladder cancer cases, including 130 among women > 10 years at their PWS. In multivariable-adjusted models, we observed nonsignificant associations among women in the highest versus lowest quartile of average drinking water nitrate concentration (HR = 1.48; 95% CI: 0.92, 2.40; ptrend = 0.11), and we found significant associations among those exposed ≥ 4 years to drinking water with > 5 mg/L NO3-N (HR = 1.62; 95% CI: 1.06, 2.47; ptrend = 0.03) compared with women having 0 years of comparable exposure. TTHM adjustment had little influence on associations, and we observed no modification by vitamin C intake. Relative to a common reference group of never smokers with the lowest nitrate exposures, associations were strongest for current smokers with the highest nitrate exposures (HR = 3.67; 95% CI: 1.43, 9.38 for average water NO3-N and HR = 3.48; 95% CI: 1.20, 10.06 and ≥ 4 years > 5 mg/L, respectively). Dietary nitrate and nitrite intakes were not associated with bladder cancer. CONCLUSIONS: Long-term ingestion of elevated nitrate in drinking water was associated with an increased risk of bladder cancer among postmenopausal women. Citation: Jones RR, Weyer PJ, DellaValle CT, Inoue-Choi M, Anderson KE, Cantor KP, Krasner S, Robien K, Beane Freeman LE, Silverman DT, Ward MH. 2016. Nitrate from drinking water and diet and bladder cancer among postmenopausal women in Iowa. Environ Health Perspect 124:1751-1758; http://dx.doi.org/10.1289/EHP191.	bladder
Expression of the p53 Inhibitors MDM2 and MDM4 as Outcome Predictor in Muscle-invasive Bladder Cancer.	AIM: To evaluate the prognostic role of the p53-upstream inhibitors MDM2, MDM4 and its splice variant MDM4-S in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: mRNA Expression levels of MDM2, MDM4 and MDM4-S were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) in 75 RC samples. Logistic regression analyses identified predictors of recurrence-free (RFS) and cancer-specific survival (CSS). RESULTS: High expression was found in 42% (MDM2), 27% (MDMD4) and 91% (MDM4-S) of tumor specimens. Increased MDM2 expression was significantly associated with higher tumor stage (p=0.05) and lymphovascular invasion (LVI) (p=0.041). In the univariate analysis, low MDM4 expression (hazard ratio (HR)=5.93; p=0.002; HR=3.00; p=0.047), but not MDM2 (HR=1.63; p=0.222; HR=1.59; p=0.27), were associated with RFS and CSS. In the multivariate analysis, the combination of low MDM4 and high MDM2 was significant for RFS and CSS (HR=14.9; p=0.001; HR=5.63; p=0.019). CONCLUSION: The combination of MDM2 and MDM4 expression is an independent predictor in patients undergoing RC for MIBC.	bladder
Impact of surgical margin status on the outcome of bladder cancer treated by radical cystectomy: a meta-analysis.	Data regarding the association between surgical margin status and the outcome of bladder cancer treated by radical cystectomy (RC) are conflicting. Therefore, the present meta-analysis was performed to assess the associations between the outcomes of bladder cancer, in terms of recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS), and the presence of positive surgical margins versus negative surgical margins following treatment with RC. Research articles published prior to April 2016 were identified from Pubmed, Embase and the Cochrane Library databases. A total of 36 articles were included, with a sample size of 38,384 bladder cancer patients. Of these, 4,354 patients were reported to have positive surgical margins. Significant associations were detected between positive surgical margins following RC and unfavorable RFS [summary relative risk estimate (SRRE), 1.63; 95% confidence interval (CI), 1.46-1.83; P = 0.105], CSS (SRRE, 1.82; 95% CI, 1.63-2.04; P = 0.001) and OS (SRRE, 1.68; 95% CI, 1.58-1.80; P = 0.805), by fixed or random effects models. The findings were consistent independently of age, sample size, publication year, follow-up duration, study type and geographical region. In summary, the present findings demonstrate that the presence of positive surgical margins is associated with poor survival outcomes in bladder cancer following RC, indicating that avoidance of positive surgical margins during surgery is helpful to improve the prognosis of patients with bladder cancer.	bladder
Study on the significance of Cofilin 1 overexpression in human bladder cancer.	PURPOSE: Cofilin 1 is a type of cytoskeletal protein. The overexpression of this gene has been regarded to hold a special relationship with the development and progress of some cancers. However, the detailed position of Cofilin 1 in human bladder cancer has not been investigated intensively. METHODS: In this study, we mainly explored the relationship between human bladder cancer and the expression of Cofilin 1. The expression of Cofilin 1 in bladder cancer tissues and paracancerous tissues of patients was evaluated with quantitative polymerase chain reaction, Western blot, and immunohistochemical staining. Downregulation of Cofilin 1 expression model was established with siRNA in human RT4 bladder cancer cell line, and the changing cell viability was analyzed to determine the role of Cofilin 1 in human bladder cancer. RESULTS: Our results showed that the expression of Cofilin 1 was much higher in both RNA level and protein level in human bladder cancer tissues than paracancerous tissues for 3 patients. Downregulation of Cofilin 1 expression could inhibit cell proliferation, cell migration, cell adhesion, and colony formation ability, and increase the percentage of cell apoptosis in RT4 cells. CONCLUSIONS: Our study indicates that Cofilin 1 holds an important position in the development and progression of human bladder cancer, and this gene might become a novel target in the diagnosis and treatment of human bladder cancer.	bladder
Targeted imaging of urothelium carcinoma in human bladders by an ICG pHLIP peptide ex vivo.	Bladder cancer is the fifth most common in incidence and one of the most expensive cancers to treat. Early detection greatly improves the chances of survival and bladder preservation. The pH low insertion peptide (pHLIP) conjugated with a near-infrared fluorescent dye [indocyanine green (ICG)] targets low extracellular pH, allowing visualization of malignant lesions in human bladder carcinoma ex vivo. Cystectomy specimens obtained after radical surgery were immediately irrigated with nonbuffered saline and instilled with a solution of the ICG pHLIP construct, incubated, and rinsed. Bladders were subsequently opened and imaged, the fluorescent spots were marked, and a standard pathological analysis was carried out to establish the correlation between ICG pHLIP imaging and white light pathological assessment. Accurate targeting of bladder lesions was achieved with a sensitivity of 97%. Specificity is 100%, but reduced to 80% if targeting of necrotic tissue from previous transurethral resections or chemotherapy are considered as false positives. The ICG pHLIP imaging agent marked high-grade urothelial carcinomas, both muscle invasive and nonmuscle invasive. Carcinoma in situ was accurately diagnosed in 11 cases, whereas only four cases were seen using white light, so imaging with the ICG pHLIP peptide offers improved early diagnosis of bladder cancers and may also enable new treatment alternatives.	bladder
Role of galectin-1 in urinary bladder urothelial carcinoma cell invasion through the JNK pathway.	Human galectin-1 is a member of the galectin family, proteins with conserved carbohydrate-recognition domains that bind galactoside. Galectin-1 is highly expressed in various tumors and participates in various oncogenic processes. However, detailed descriptions of the function of galectin-1 in urinary bladder urothelial carcinoma have not been reported. Our previous cohort investigation showed that galectin-1 is associated with tumor invasiveness and is a possible independent prognostic marker of urinary bladder urothelial carcinoma. The present study aimed to clarify the relevance of galectin-1 expression level to tumor progression and invasion. In order to decipher a mechanism for the contribution of galectin-1 to the malignant behavior of urinary bladder urothelial carcinoma, two bladder cancer cell lines (T24 and J82) were established with knockdown of galectin-1 expression by shRNA. Bladder cancer cells with LGALS1 gene silencing showed reduced cell proliferation, lower invasive capability, and lower clonogenicity. Extensive signaling pathway studies indicated that galectin-1 participated in bladder cancer cell invasion by mediating the activity of MMP9 through the Ras-Rac1-MEKK4-JNK-AP1 signaling pathway. Our functional analyses of galectin-1 in urinary bladder urothelial carcinoma provided novel insights into the critical role of galectin-1 in tumor progression and invasion. These results revealed that silencing the galectin-1-mediated MAPK signaling pathway presented a novel strategy for bladder cancer therapy.	bladder
Cytologic persistence of malignant cells after transurethral resection of bladder tumors: Implications for concomitant manipulation of the urinary tract at the time of endoscopic resection.	BACKGROUND: The current study was conducted to determine the feasibility of cytologically clearing the bladder of tumor cells after transurethral resection of bladder tumor (TURBT) and aggressive serial bladder washing. METHODS: A prospective pilot sample of 20 patients with known bladder masses was enrolled before undergoing TURBT. Preoperative cytology and 4 postoperative cytology specimens were assessed for malignant cells between serial bladder washes. Surgeons assessed tumor grade visually at the time of TURBT. RESULTS: Surgeons were able to differentiate high-grade disease with limited accuracy (75% sensitivity, 92% specificity, 85% negative predictive value, and 86% positive predictive value). For patients with low-grade disease (12 patients), cytology was atypical in 25% of patients immediately before TURBT and was negative after serial washings in all patients. In patients with high-grade disease (8 patients), approximately 75% had cytology consistent with high-grade urothelial carcinoma immediately before TURBT and only 1 patient was cleared cytologically after serial bladder washings. CONCLUSIONS: In patients with high-grade disease, serial bladder washing after TURBT does not appear to clear malignant cells as detected by cytology. This theoretical oncologic risk should be weighed when considering concomitant upper tract procedures such as retrograde pyelography. Future work is needed to quantify risk. Cancer Cytopathol 2017;125:114-119. © 2016 American Cancer Society.	bladder
Robotic Intracorporeal Padua Ileal Bladder: Surgical Technique, Perioperative, Oncologic and Functional Outcomes.	BACKGROUND: Robot-assisted radical cystectomy (RARC) with intracorporeal neobladder reconstruction is a challenging procedure. The need for surgical skills and the long operative times have led to concern about its reproducibility. OBJECTIVE: To illustrate our technique for RARC and totally intracorporeal orthotopic Padua ileal bladder. DESIGN, SETTING, AND PARTICIPANTS: From August 2012 to February 2014, 45 patients underwent this technique at a single tertiary referral centre. SURGICAL PROCEDURE: RARC, extended pelvic lymph node dissection, and intracorporeal partly stapled neobladder. Surgical steps are demonstrated in the accompanying video. MEASUREMENTS: Demographics, clinical, and pathological data were collected. Perioperative, 2-yr oncologic and 2-yr functional outcomes were reported. RESULTS AND LIMITATIONS: Intraoperative transfusion or conversion to open surgery was not necessary in any case and intracorporeal neobladder was successfully performed in all 45 patients. Median operative time was 305min (interquartile range [IQR]: 282-345). Median estimated blood loss was 210ml (IQR: 50-250). Median hospital stay was 9 d (IQR: 7-12). The overall incidence of perioperative, 30-d and 180-d complications were 44.4%, 57.8%, and 77.8%, respectively, while severe complications occurred in17.8%, 17.8%, and 35.5%, respectively. Two-yr daytime and night-time continence rates were 73.3% and 55.5%, respectively. Two-yr disease free survival, cancer specific survival, and overall survival rates were 72.5%, 82.3%, and 82.4%, respectively. The small sample size and high caseload of the centre might affect the reproducibility of these results. CONCLUSIONS: Our experience supports the feasibility of totally intracorporeal neobladder following RARC. Operative times and perioperative complication rates are likely to be reduced with increasing experience. PATIENT SUMMARY: We report the outcomes of our first 45 consecutive patients who underwent robot-assisted radical cystectomy with intracorporeal neobladders. Perioperative, oncologic, and functional outcomes support this technique as a feasible and safe surgical option in tertiary referral centres.	bladder
Green-light laser en bloc resection for primary non-muscle-invasive bladder tumor versus transurethral electroresection: A prospective, nonrandomized two-center trial with 36-month follow-up.	OBJECTIVES: To evaluate the safety and efficacy of LBO laser en bloc resection compared with transurethral electroresection (TURBT) for the treatment of primary non-muscle-invasive bladder tumors. METHODS: From September 2010 to February 2012, a prospective, nonrandomized two-center trial was performed. A total of 158 patients (83 underwent laser resection and 75 TURBT) were included in the present study. The preoperative, intraoperative, and postoperative clinical characteristics were recorded and compared in the two groups. RESULTS: There were no differences with the preoperative characteristics between the patients in the two groups. The mean operative time was 21.46 ± 10.42 minutes for laser resection and 27.47 ± 15.30 minutes for TURBT (P = 0.004). LBO laser group was also associated with less hemoglobin decrease compared with TURBT group (0.87 ± 0.28 g/ml vs. 1.00 ± 0.33 g/ml, P = 0.009). Obturator nerve reflection was absent during laser resection, whereas was observed in nine patients during TURBT (P = 0.001). Two patients in the TURBT group suffered bladder perforation. Three patients in TURBT group and one patient in LBO laser group experienced urethral stricture. The recurrence-free survival rate did not differ significantly between two groups after 36 months follow-up. CONCLUSIONS: The results of our trial have shown that LBO laser en bloc resection is feasible, safe, and effective alternative for the treatment of primary non-muscle-invasive bladder tumors. Besides, it can provide intact specimen for the pathologic diagnosis. Lasers Surg. Med. 48:859-865, 2016. © 2016 Wiley Periodicals, Inc.	bladder